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A.R. Ahmed, M.S. Razzaque, B. Ahmed, E.A. Khan, M.E. Meniconi,, C.S. Foster; Role of IL-4 in the Pathogenesis of Ocular Cicatricial Pemphigoid . Invest. Ophthalmol. Vis. Sci. 2003;44(13):3790.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Increased stromal accumulation of macrophages and submucosal fibrosis due to excessive accumulation of collagens are important histological features in ocular cicatricial pemphigoid (OCP). Interleukin 4 (IL-4) plays an important role in both the inflammatory and fibrotic events in human and experimental diseases. We have examined the possible role of IL-4 in pathogenesis of ocular cicatricial pemphigoid (OCP). Methods: Conjunctiva biopsy tissues of patients with OCP and control subjects were studied for the expression of IL-4. Conjunctival fibroblasts isolated from normal controls and patients with OCP were also studied for the expression of IL-4. To examine the effects of IL-4 in the induction of inflammatory and fibrogenic factors, conjunctival fibroblasts were treated with various concentrations of IL-4; the expression levels of macrophage colony-stimulating factor (m-CSF), heat shock protein 47 (HSP47) and type I collagen was determined, by quantitative real-time PCR, and ELISA. The level of IL-4 was also studied in serum samples obtained from patients with OCP during active diseases and remission, and controls, using ELISA. Results: Compared to the weak expression of IL-4 in the normal conjunctiva, an increased expression of IL-4 was noted in biopsies obtained from conjunctiva of OCP patients. Similar increase in the expression of IL-4 was also detected in fibroblasts isolated from conjunctiva of OCP patients, compared to normal conjunctival fibroblasts. A significantly increased level of m-CSF both at the mRNA (by real-time PCR) and protein level (by ELISA) was detected in IL-4-stimulated cells. Similarly, IL-4 treatment resulted in the induction of type I collagen and collagen-binding HSP47 by conjunctival fibroblasts, as detected by real-time PCR. No apparent changes in the levels of IL-4 were detected in serum samples of patients with OCP and controls, using ELISA. Conclusions: Increased conjunctival expression of IL-4 may play an important role in the regulation of local accumulation of macrophages (by inducing m-CSF), and matrix accumulation (by inducing HSP47 and collagen) during conjunctival scarring in patients with OCP. IL-4, therefore, may augment or enhance both conjunctival inflammatory and subsequent fibrotic responses in patients with OCP.
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